POS0521 RISKS OF SEVERE INFECTION AFTER THE INTRODUCTION OF bDMARDs IN NEWLY DIAGNOSED RHEUMATOID ARTHRITIS PATIENTS: A POPULATION-BASED INTERRUPTED TIME-SERIES ANALYSIS
Authors: Y. V. Zhou, D. Lacaille, N. Lu, J. Kopec, Y. Qian, B. Nosyk, J. A. Aviña-Zubieta, J. Esdaile, H. Xie
Journal: Annals of the Rheumatic Diseases (2022)

Background Biological disease-modifying anti-rheumatic drugs (bDMARDs) are effective in suppressing inflammation and preventing joint damage. But bDMARDs may be associated with increased risk of severe infection. Evidence on this is contradictory with some studies showing increased risk, whereas others reporting no significant changes. Objectives To determine the impact of the introduction of bDMARDs on severe infection among patients newly diagnosed with RA compared with non-RA individuals. Methods In this age- and gender-matched cohort study using administrative health data for the population of BC, Canada, all incident RA patients diagnosed between 1995–2007 were identified. Non-RA individuals were randomly selected from the general control population to match with RA. Incident RA/non-RA individuals were then divided into quarterly cohorts according to their diagnosis date. Two outcomes were examined: (1) first severe infection (FSI) after RA onset necessitating hospitalization or occurring during hospitalization; and (2) all severe infections (ASI) after RA onset. We calculated the 8-year FSI and ASI rate for each cohort. We conducted interrupted time-series analyses to compare levels and trends of FSI and ASI in RA and non-RA individuals diagnosed during pre-bDMARDs (1995–2001) and post-bDMARDs (2003–2007) periods. Adjusted 8-year FSI and ASI rates for RA and non-RA cohorts diagnosed five years after bDMARDs introduction were compared with expected rates assuming no bDMARDs introduction, based on extrapolation of pre-bDMARDs trends. Results A total of 60,226 and 588,499 incident RA/non-RA individuals were identified. We identified 8,954 FSI and 14,245 ASI in RA, and 56,153 FSI and 79,819 ASI in non-RA. The 8-year FSI rates among RA patients diagnosed in the pre-bDMARDs period decreased over time but leveled off among those diagnosed in the post-period (Figure 1). The adjusted difference between the post- and pre-bDMARDs secular trends of 8-year FSI rates was 0.68 (p=0.03) in RA and 0.03 (p=0.67) in non-RA (Table 1). The 8-year ASI rates among RA patients diagnosed in the pre-bDMARDs period decreased over time but increased significantly among those diagnosed in the post-period (Figure 1). The adjusted difference between the post- and pre-bDMARDs secular trends of 8-year ASI rates was 1.85 (p=0.001) in RA and 0.12 (p=0.29) in non-RA (Table 1). For RA cohort diagnosed 5 years after bDMARDs introduction, ASI rate increased by 20.4% than expected rates assuming no bDMARDs introduction. In contrast, ASI rate in non-RA increased by only 10.9%. Table 1. Results of interrupted time-series analysis of FSI/ASI rates, adjusting for age, gender, chronic obstructive pulmonary disease, Romano Charlson Comorbidity Index, diabetes, chronic kidney diseases, alcoholism, cancer, prior hospitalization with infection and socio-economic status at disease diagnosis year, using stepwise model selection Outcome Parameter RA Non-RA Unadj. Diff (95% CI) Adj. Diff (95% CI) Unadj. Diff (95% CI) Adj. Diff (95% CI) p-value p-value p-value p-value FSI Trend 0.63 (0.03, 1.22) 0.0441 0.68 (0.09, 1.27) 0.0292 0.08 (-0.08, 0.25) 0.3237 0.03 (-0.12, 0.19) 0.6728 Level (1 year post-intervention) 0.50 (-2.00, 2.99) 0.6989 0.31 (-1.88, 2.49) 0.7847 0.41 (-0.21, 1.03) 0.2041 0.26 (-0.24, 0.75) 0.3103 5 years post-intervention 3.01 (-0.85, 6.87) 0.1331 3.02 (-0.48, 6.52) 0.0986 0.75 (-0.24, 1.73) 0.1433 0.39 (-0.46, 1.25) 0.3721 ASI Trend 1.84 (0.83, 2.84) 0.0009 1.85 (0.81, 2.89) 0.0011 0.28 (0.04, 0.53) 0.0305 0.12 (-0.10, 0.34) 0.2877 Level (1 year post-intervention) -1.21 (-5.41, 3.00) 0.5763 -1.44 (-5.44, 2.56) 0.4850 1.46 (0.42, 2.49) 0.0085 1.20 (0.38, 2.02) 0.0064 5 years post-intervention 6.14 (0.26, 12.01) 0.0466 5.97 (0.02, 11.93) 0.0560 2.60 (1.08, 4.12) 0.0017 1.69 (0.45, 2.92) 0.0109 Figure 1. Unadjusted rates. Conclusion Arthritis onset after bDMARDs introduction is associated with an elevated risk of severe infection in RA patients, compared with matched non-RA individuals. Acknowledgements We would like to thank the Ministry of Health of British Columbia and Population Data BC for providing access to the administrative data. All inferences, opinions, and conclusions drawn in this publication are those of the authors, and do not reflect the opinions or policies of the Data Stewards or the [British Columbia] Ministry of Health. No personal identifying information was made available as part of this study. Procedures used were in compliance with British Columbia’s Freedom in Information and Privacy Protection Act. Ethics approval was obtained from the University of British Columbia’s Behavioral Research Ethics Board (H15-00887). Disclosure of Interests None declared.